The organization of membrane-spanning proteins within discrete microdomains is critical for their physiologic function. This is especially important in the heart, where ion transporter and force-transducing microdomains are responsible for excitation-contraction coupling, anisotropic depolarization, and mechanotransduction. The following review will discuss recent advances in our understanding of the patterning of ion channel and force-transmitting membrane microdomains in cardiomyocytes, focusing on the T-tubule and intercalated disc.