Ion channel biology offers great opportunity in identifying and learning about cardiac pathophysiology mechanisms. The discovery of transient receptor potential (TRP) channels is an add-on to the opportunity. Interacting with numerous signaling pathways, being activated multimodally, and having prescribed signatures underlining acute hemodynamic control and cardiac remodeling, TRP channels regulate cardiac pathophysiology. Impaired Ca2+-handling cause contractile abnormality. Modulation of intracellular Ca2+ concentration ([Ca2+]i) is a major part of Ca2+-handling processes in cardiac pathophysiology. TRP channels including TRPM4 regulate [Ca2+]i, Ca2+-handling and cardiac contractility. The channels modulate flux of divalent cations, such as Ca2+ during Ca2+-handling and cardiac contractility. Seminal works implicate TRPM4 and TRPC families in intracellular Ca2+ homeostasis. Defective Ca2+-homeostasis through TRP channels interaction with Ca2+-dependent regulatory proteins such as sodium calcium exchanger (NCX) results in abnormal Ca2+ handling, contractile dysfunction and in spontaneous ectopy. This review provides insight into TRP channels mediated pathological Ca2+-handling and spontaneous ectopy.