It is no surprise that regular exercise is good for you, but the molecular mechanisms behind the health benefits remain poorly understood. In this week’s issue, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) seeks to address this by profiling a range of changes that take place during endurance exercise. Working with male and female rats, the researchers measured changes to the transcriptome, epigenome, proteome, metabolome, lipidome and immunome in a broad array of tissues across eight weeks of treadmill-based exercise. They identified thousands of molecular changes that collectively offer insight into the benefits accrued to immune, metabolic and stress-response pathways as the body adapts to exercise.