BACKGROUND Heterocycles play a major role in many fields of biochemical and physiological such as amino acids, DNA bases, vitamins, endogenous neurotransmitters, etc. Nitrogencontaining heterocyclic compounds play a vital role in medicinal chemistry and exhibit notable biological and pharmacological activities. In the past two decades, scientists focused more on the diverse biological activities of pyrimidine derivatives. Pyrimidine is a six-membered heterocyclic compound, and it is present naturally in nucleic acid components (uracil, thymine, and cytosine) and vitamin B1; it is a promising lead molecule for synthesising compounds with various substitutions to treat various diseases. OBJECTIVE We focused on the structure-activity relationship of pyrimidine derivatives and its various biological activities reported from 2010 to date. RESULTS From this review, we concluded that the position of substituents in the pyrimidine nucleus greatly influences biological activities. Thus, the pyrimidine nucleus showed anti-microbial, anticancer, anti-inflammatory, anti-tubercular, anti-convulsant, antihypertensive, anthelmintic, antidepressant, analgesic, anti-hyperglycemic activities, etc. Conclusion: This study provides an overview of the pyrimidine nucleus and its derivatives from 2010 to date. There is a future scope for identifying a lead molecule for the target biological activity.