Numerous RNA-binding proteins (RBPs) are expressed in the heart, and mutations in several RBPs have been implicated in cardiovascular disease through genetic associations, animal modeling, and mechanistic studies. However, the functions of many more cardiac RBPs, and their relevance to disease states, remain to be elucidated. Recently, we have initiated studies to characterize the functions of the RBPs RBPMS and RBPMS2 in regulating myocardial biology in zebrafish and higher vertebrate species. These studies began when we learned, using an unbiased gene discovery approach, that rbpms2a and rbpms2b in zebrafish are robust markers of embryonic myocardium. This observation, which is consistent with published data, suggests that the encoded proteins are likely to be performing critical functions in regulating one or more aspects of cardiomyocyte differentiation, proliferation, survival, and/or contractility. This notion is supported by recent reports demonstrating that zebrafish embryos with disrupted Rbpms2 function exhibit gross signs of cardiac distress. Interestingly, a 20-year-old study determined that myocardial tissue from the frog, chick, and mouse also express high levels of Rbpms and/or Rbpms2, which is suggestive of evolutionary conservation of function. In this review, we will provide a historical account of how RBPMS and RBPMS2 genes were discovered, attempt to clarify some potentially confusing nomenclature, and summarize published observations that inform our ongoing studies.