CVB3 myocarditis can lead to dilated cardiomyopath (DCM). DCM is one of the leading causes of the need for heart transplantation, so it is important to understand the life cycle of CVB3 and its interactions with the host cell. Infection causes rapid death of host cardiomyocytes by altering normal cellular homeostasis for the efficient release of progeny virion. In this chapter, we will examine the impact that CVB3 replication has on host cell biology, from events that take place at receptor ligation to progeny virus release. The primary focus will be on the myriad of signalling pathways that are activated at all stages of virus replication and their downstream effects. We will also discuss some of the extracellular effects of infection as well as immune and matrixmetalloprotease activation. Interactions of host cell proteins with the 5' untranslated region (UTR) are required for translation and replication of CVB3. These interactions do not always benefit the virus since the interactions of a 28-kDa host protein with the 5' UTR are thought to be responsible for inhibitory activity against CVB3. Finally, we will discuss how the elucidation of the different stages of replication has provided the opportunity to develop novel strategies for combating CVB3 infection.