Daily dynamics in the composition and function of the human gut microbiota have been recognized since 2014, yet the molecular mechanisms underlying these rhythms and their impact on human health remain unclear. Disrupted microbial oscillations are increasingly linked to metabolic diseases such as obesity and type 2 diabetes, and to inflammatory conditions in the gut and beyond. We propose advancing from observational studies to experimentally targeting microbial rhythms and clocks to uncover causal relationships. In vivo and in vitro models offer opportunities to uncover how signaling cues and dietary patterns influence microbial oscillations and, in turn, host metabolic and immune functions. Manipulating microbial rhythmicity independent of host physiology represents a new frontier for microbiota-based strategies to promote health and prevent diseases.