Mitochondria play a fundamental role in regulating a variety of complex metabolic processes to maintain adequate energy balance for cellular existence. To orchestrate these functions, an undisturbed mitochondrial dynamics is imperative through a set of tightly guided mechanisms. Interference in key signature processes by several genetic, epigenetic and age-linked factors triggers mitochondrial dysfunction through decrease in mitochondrial biogenesis, reduced mitochondrial content, aberrant mtDNA mutations, increased oxidative stress, deficient mitophagy, energy dysfunction, decrease in anti oxidant defense and impaired calcium homeostasis. Mitochondrial dysfunction is widely implicated in origin and development of various age associated degenerative human ailments including metabolic syndromes, cardiovascular diseases, cancer, diabetes and neurodegenerative disorders. The present review revisits the mitochondrial anomalies involved in aetiology of different human diseases and also highlights the translational significance of nano-vectors aimed for selective mitochondrial engineering which might pave way for development of novel therapeutics.