The sarcolemmal membrane of mammalian cardiac ventricular myocytes is characterized by the presence of invaginations called transverse tubules (t-tubules). Transverse tubules occur at the Z-line as transverse elements with longitudinal extensions. While the existence of t-tubules has been known for some time, recent experimental studies have suggested that their structure and function are more complex than previously believed. There are, however, aspects of t-tubule function that are not currently amenable to experimental investigation, but can be investigated using computational and mathematical approaches. Such studies have helped elucidate further the possible role of t-tubules in cell function. This review summarizes recent experimental and complementary computational studies which highlight the important role of t-tubules in cardiac excitation-contraction coupling.