The reggies/flotillins are oligomeric scaffolding proteins for membrane microdomains. We show here that reggie‐1/flotillin‐2 microdomains are organized along cortical F‐actin in several cell types. Interaction with F‐actin is mediated by the SPFH domain as shown by in vivo co‐localization and in vitro binding experiments. Reggie‐1/flotillin‐2 microdomains form independent of actin, but disruption or stabilization of the actin cytoskeleton modulate the lateral mobility of reggie‐1/flotillin‐2 as shown by FRAP. Furthermore, reggie/flotillin microdomains can efficiently be immobilized by actin polymerisation, while exchange of reggie‐1/flotillin‐2 molecules between microdomains is enhanced by actin disruption as shown by tracking of individual microdomains using TIRF microscopy.