(142 words)Modern human environments are vastly different to those of our forebears. Rapidly advancing technology in transportation, communications, workplaces and home entertainment confer a wealth of benefits, but increasingly come with costs to human health.Sedentary behaviour -too much sitting as distinct from too little physical activitycontributes adversely to cardiometabolic health outcomes and premature mortality. Findings from observational epidemiology have been synthesised in meta-analyses and evidence is now shifting into the realm of experimental trials with the aim of identifying novel mechanisms and potential causal relationships. We discuss recent observational and experimental evidence that makes a compelling case for reducing and breaking up prolonged sitting time in both the primary-prevention and disease management contexts. We also highlight future research needs, the opportunities for developing targeted interventions, and the potential of population-wide initiatives designed to address too much sitting as a health risk.