AbstractMembers of the myosin superfamily of molecular motors are large mechanochemical ATPases that are implicated in an ever-expanding array of cellular functions. This review focuses on mammalian nonmuscle myosin-2 (NM2) paralogs, ubiquitous members of the myosin-2 family of filament-forming motors. Through the conversion of chemical energy into mechanical work, NM2 paralogs remodel and shape cells and tissues. This process is tightly controlled in time and space by numerous synergetic regulation mechanisms to meet cellular demands. We review how recent advances in structural biology together with elegant biophysical and cell biological approaches have contributed to our understanding of the shared and unique mechanisms of NM2 paralogs as they relate to their kinetics, regulation, assembly, and cellular function.