This article recapitulates the existing in vitro and in vivo studies focusing on the effects of neferine-an alkaloid derivative of lotus plant, in various disease models and its effects on key signaling molecules. The review also compiles a large number of research studies that demonstrate methods for isolation and extraction, biosynthetic pathway, pharmacological activity and mode of action of neferine and their underlying mechanisms at cellular level. Neferine is a unique bis-benzylisoquinoline alkaloid that possesses a number of therapeutic effects such as anti-cancer, anti-diabetic, anti-aging, anti-microbial, anti-thrombotic, anti-arrhythmic, anti-inflammatory and even anti-HIV. It also enhances the anti-cancer properties of other anti-cancer drugs like cisplatin, adriamycin, taxol, etc. It is also reported to reverse chemo-resistance and enhance sensitivity of the cancer cells towards anti-cancer drugs. The underlying mechanisms for its activities mainly include apoptosis, autophagy and G1 arrest. Neferine protects them against the effect of drugs like cisplatin. The therapeutic properties of neferine is widely diverse, while it shows toxicity to cancer it also shows cyto-protective effects against cardio-vascular diseases, pulmonary disease, and is also effective against Alzheimer's disease and elicits anti-oxidative effect in many cellular systems. This article thus is the first ever attempt to review the therapeutic activities of neferine established in in vitro and in vivo models and to compile all the fragmented data available on the omnipotent activities of neferine.