Pyrimidines have emerged as a crucial building block in drug development over the past six decades, with significant advancements in their therapeutic applications. This review highlights recent progress in pyrimidine-based drugs, focusing on their impact in various therapeutic areas, including anti-infectives, anticancer agents, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article discusses the synthesis of medicinal agents, the biological targets they address, and their pharmacokinetic and pharmacodynamic properties. Pyrimidines are noted for their versatility, improved medicinal chemistry properties, and ability to act as bioisosteres for phenyl and other aromatic π systems. The review covers recent studies on pyrimidine-based drugs for treating infections, such as tuberculosis, fungal infections, and viral infections, as well as their use in cancer therapy, particularly in targeting breast cancer, lung cancer, and microtubule disruption. The biological potency, ADME properties, and pharmacokinetic/pharmacodynamic data of these compounds are discussed, emphasizing their potential in addressing previously untreatable medical conditions.Pyrimidines have emerged as a crucial building block in drug development over the past six decades, with significant advancements in their therapeutic applications. This review highlights recent progress in pyrimidine-based drugs, focusing on their impact in various therapeutic areas, including anti-infectives, anticancer agents, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article discusses the synthesis of medicinal agents, the biological targets they address, and their pharmacokinetic and pharmacodynamic properties. Pyrimidines are noted for their versatility, improved medicinal chemistry properties, and ability to act as bioisosteres for phenyl and other aromatic π systems. The review covers recent studies on pyrimidine-based drugs for treating infections, such as tuberculosis, fungal infections, and viral infections, as well as their use in cancer therapy, particularly in targeting breast cancer, lung cancer, and microtubule disruption. The biological potency, ADME properties, and pharmacokinetic/pharmacodynamic data of these compounds are discussed, emphasizing their potential in addressing previously untreatable medical conditions.