Mitochondrial flux, the processes by which the mitochondrial compartment of the cell fuses, fissions and is degraded, underlies a complex spectrum of diseases. Pathological functioning of the innate immune system is underpinned by signalling pathways previously studied for their role reconfiguring cellular metabolic requirements. This review attempts to establish the physiologic state of mitochondrial flux across the cell, explain the process and regulation of mitochondrial biogenesis and autophagic degradation, before examining how disruption of these processes is intrinsic to a number of disease states. Particular attention is paid to how bioenergetic demands of the tissues are modulated in viral SARS-CoV, hepatitis B & C infection and asthma.