Monoamine oxidases are the crucial drug target for the treatment of neurodegenerative disorders like depression, Parkinson’s disease, and Alzheimer’s disease. The enzymes catalyze the oxidative deamination of several monoamine containing neurotransmitters, i.e. serotonin (5-HT), melatonin, epinephrine, norepinephrine, phenylethylamine, benzylamine, dopamine, tyramine, etc. The oxidative reaction of monoamine oxidases results in the production of hydrogen peroxide that led to the neurodegeneration process. Therefore, the inhibition of monoamine oxidases has shown a profound effect against neurodegenerative diseases. At present, the design and development of newer lead molecules for the inhibition of monoamine oxidases is under the progress of intensive research in the field of medicinal chemistry. Recently, the advancement in QSAR methodologies has shown considerable interest in the development of monoamine oxidase inhibitors. The present review describes the development in QSAR methodologies, its role in the design of newer monoamine oxidase inhibitors. It will assist the medicinal chemist in the identification of selective and potent monoamine oxidase inhibitors from various chemical scaffolds.