The Keystone Symposia conference on positive-strand RNA viruses provides an international forum for research on human, animal, insect, plant and bacterial viruses with positive-strand RNA genomes. This group of viruses contains many clinically relevant and well-known pathogens (e.g., Enterovirus 71, hepatitis C virus, Dengue and West Nile virus, and Coronaviruses). Given their high rates of mutation and their capacity for zoonosis, positive-strand RNA viruses represent constant threats to the global human population, as evidenced by the recent Zika virus (ZIKV) epidemic and the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Detailed analyses into viral transmission and spread, evolution and epidemiology, tissue tropism, host immune response and viral countermeasures, as well as the development of novel antiviral therapeutics and vaccines is critical to combat these viruses. This conference brings together experienced and junior experts to share their latest findings in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development applied to the field of positive-strand RNA viruses. There are no other conferences solely focused on positive-strand RNA viruses. Smaller conferences (e.g. the European Picornavirus (EuroPic) focus on select virus families while other very large conferences (e.g. the American Society for Virology (ASV)) focus on nearly all viral species. The very focused nature of smaller conferences and the very diffuse nature of very large conferences both limit the ability of experts specializing in complementary but non-overlapping areas to share their research, establish new collaborative efforts, and gain insights into the latest findings of others in the field.