The isoquinoline compounds from alkaloidal class have been excellent source of important phytoconstituents having wide range of pharmacological activities. Berberine is a protoberberine alkaloidal compound obtained from Berberis genus plants which belongs to family Barberidaceae. Due to its unique structural properties, berberine and its derivatives has been exploited extensively for its potential uses in various pharmacological targets such as cancer, inflammation, diabetes, gastrointestinal disorder, viral and microbial infections, neurological disorder like Alzheimer, anxiety, schizophrenia, depression, etc. This review illustrates the updated information on berberine with respect to its isolation, biosynthesis, chemical synthesis, structural modification and pharmacological activities. An extensive literature search were carried out in various search engine like PubMed, Google Scholars, Research Gate and SCOPUS by using keywords like Berberine, protoberberine alkaloids, isoquinoline derivatives, pharmacological effects, etc. Prephenic acid is the starting material for biosynthesis of berberine. Structural modifications lead to generation of various potential derivatives, which earn patents by researchers. Besides toxicities, the complications of low solubility and bioavailability should be eliminated. To improve its safety, efficacy and selectivity the berberine should be carefully derivatized.