Huntington’s disease (HD) was initially described in 1872 by George Huntington (an American physician). HD is a progressive neurodegenerative disease characterized by chorea, cognitive, psychiatric and motor impairments with extreme phenotypes that include irregular circadian rhythm, weight reduction and muscle atrophy. The global distribution of this progressive neurodegenerative disease is reported to be 2.71 in 100,000 individuals. Since HD manifestations become apparent in mid or later stages of life, the individuals in their mid-life who are unaffected carriers of HD gene mutations could have passed on to their offsprings resulting in the existence of substantial population of young mutant huntington (Htt) carriers who are currently asymptomatic and undiagnosed for HD. Notably, aggregation of intracellular mutant Htt with neurotoxic outcomes is stated to be a significant hallmark of HD. Considering its genetic predictability, HD could be one of the most perceptive neurodegenerative diseases to early intervention. This makes HD as a potent model system to develop therapeutic interventions for other similar neurodegenerative diseases. Taken together, this comprehensive review is intended to cover all aspects of this fatal and dynamic autosomal dominant neurodegenerative disorder including pathogenesis, inter-correlation of various molecular signaling pathways involved in HD progression, preclinical HD animal models, various therapeutic interventions and HD associated diagnostic biomarkers.