Twenty years ago, we did things a little differently at the Nature Methods office. We printed out submitted manuscripts and scribbled notes in the margins; we marked changes in proofs with a red pen. The trill of a landline telephone ringing was our background soundscape. And when authors agreed to share their software to be peer-reviewed, they sent us multiple copies on CD (that’s a compact disk, for you young readers), which we then shipped to reviewers.

Although much has changed in two decades, the core of what Nature Methods strives to be as a research journal has not deviated. Our very first Editorial1 boldly declared our overarching goal of disseminating innovative research methods for their own sake. “When the concept for the journal was first proposed, there was a strong dose of skepticism that a journal focused on methods instead of biological insight could carry the Nature brand,” recalls Veronique Kiermer, the inaugural chief editor of Nature Methods (her current role is chief scientific officer at PLOS). “This was still a time when a methods paper was ‘just a methods paper’ … I thought Nature Methods was an opportunity to change that and to give methods developers the credit they deserved.”

We have lost count of the number of times that we have heard that experimental methods development, software tool development, method performance comparison studies or the generation of resources is not ‘real science’ — that doing real science means generating novel scientific knowledge. But just like any hypothesis-driven research project, the work that our authors do involves much creativity, ingenuity and perseverance. We continue to strongly believe in Kiermer’s original vision that new methods, tools and technology drive scientific progress, and this important work is real science and deserves to be funded, recognized, highlighted and celebrated for its own sake.

In this special anniversary issue, we shine a light on our authors, many of whom were graduate students or postdoctoral researchers in the early days of Nature Methods and are now at the midpoints of their careers. In the Technology Feature, several authors share with journalist Vivien Marx their stories of how their publications in Nature Methods shaped their careers as well as the direction of research in their respective fields. And in this month’s Lab & Life column, scientists describe how taking risks can have big payoffs in methods development research.

Nature Methods has always set a high bar for the reporting of novel methods — this also has not changed over the past two decades. As we place a strong emphasis on method practical and general applicability, transparent dissemination and strong validation are key. “Because of the practical focus of Nature Methods, we also did a lot of work to support the transparency of methods reporting — we worked with researchers to establish standards, we demanded the sharing of data, code and reagents, and we promoted protocols as bona fide research outputs,” says Kiermer. “We wanted ‘methods that work’, and for that we needed openness and transparency.”

This month we also shine a light on the important work of our editorial team. We invited Nature Methods’ former and current manuscript editors and chief editors to contribute personal essays that showcase some of their accomplishments at the journal. For many of us, commissioning and editing a ‘Method of the Year’ special issue or a Focus issue has been a personal highlight. Our editors also highlighted journal initiatives such as our Points of Significance column, developed to educate readers on statistical concepts (the latest of which you can read in this issue); the adoption of a Registered Reports format as an alternative model for peer review of method performance comparison studies; and our publication of reporting standards that set a high bar for reproducible and transparent research in various fields in biology. We invite you to read this Feature, which provides a window into our proudest memories and our excitement about future methods development research.

As we browse through our first issue, published in October 2004, it is truly astounding to ponder the technological leaps that have been made in life sciences research. Twenty years ago, there was no high-throughput, cost-effective DNA or RNA sequencing. The diffraction barrier in fluorescence imaging had not yet been broken. Cryo-electron microscopy data were used to reconstruct low-resolution protein ‘blobs’. There were no organoids and no CRISPR, and very few people talked about single cells. Our journal has published many important contributions that have helped to advance basic research in the life sciences, and we remain as proud as ever to be a leading forum for disseminating new methods, tools and techniques. We can’t wait to see what the next 20 years has in store.

We give a heartfelt thank you to our authors, reviewers and readers — your work, your diligence and your creativity have powered the past 20 years — and we are grateful for your support! Please join us in a toast to 20 years!