Myosins are represented by a wide range of different classes of molecule, of which the most extensively studied are the class II myosins which drive muscle contraction and cell organization; the functional unit of class II myosins comprises two myosin heavy chains (MHCs). This minireview gives an update on class II MHCs of nematodes and describes a comparative analysis of MHC genes from nematodes and other organismal groups. Genetic analyses of sequence data for the four functional domains of MHCs (i.e., the SH3-like N-terminal, head, neck and tail domains) reveal a delineation between both the nematode and non-nematode myosins and between muscle and non-muscle myosins. The distinctiveness of the MHCs of nematodes suggests functional and tissue specialization. The elucidation of the functional roles of myosins and other molecules in specific signaling pathways in nematodes has the potential to lead to new intervention strategies for parasites via the specific disruption or interruption of key developmental processes, having biotechnological implications in the longer term.