This review summarizes recent advances in pyrimidine-based drugs, highlighting their diverse applications in drug discovery for various therapeutic areas, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes. Pyrimidines, as a core structure in many drug molecules, have shown significant biological activity due to their synthetic accessibility, structural diversity, and ability to interact with various biological targets through hydrogen bonding and as bioisosteres for aromatic systems. The review discusses the synthesis of pyrimidine-based drugs, their biological potency, ADME properties, and pharmacokinetics/pharmacodynamics. It also emphasizes the versatility of pyrimidine-based drugs not only for their potency and affinity but also for their improved medicinal chemistry properties as bioisosteres for phenyl and other aromatic π systems. The review covers recent developments in pyrimidine-based drugs for the treatment of infections, including antibacterials, antifungals, and antivirals. For example, compounds targeting tuberculosis, fungal infections, and HIV have been developed, showing promising results in terms of activity and pharmacokinetic profiles. In the field of cancer, pyrimidine-based drugs have been explored for their ability to inhibit key signaling pathways, such as FAK and EGFR, and to target specific mutations in cancer cells. The review also discusses the development of next-generation EGFR inhibitors and CDK inhibitors, which are crucial for treating advanced or metastatic cancers. Additionally, pyrimidine-based drugs have been investigated for their potential in targeting microtubules, which are essential components of the cytoskeleton and important targets for anticancer drugs. The review highlights the importance of pyrimidine-based drugs in drug research and development, emphasizing their potential for treating previously untreatable medical conditions.This review summarizes recent advances in pyrimidine-based drugs, highlighting their diverse applications in drug discovery for various therapeutic areas, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes. Pyrimidines, as a core structure in many drug molecules, have shown significant biological activity due to their synthetic accessibility, structural diversity, and ability to interact with various biological targets through hydrogen bonding and as bioisosteres for aromatic systems. The review discusses the synthesis of pyrimidine-based drugs, their biological potency, ADME properties, and pharmacokinetics/pharmacodynamics. It also emphasizes the versatility of pyrimidine-based drugs not only for their potency and affinity but also for their improved medicinal chemistry properties as bioisosteres for phenyl and other aromatic π systems. The review covers recent developments in pyrimidine-based drugs for the treatment of infections, including antibacterials, antifungals, and antivirals. For example, compounds targeting tuberculosis, fungal infections, and HIV have been developed, showing promising results in terms of activity and pharmacokinetic profiles. In the field of cancer, pyrimidine-based drugs have been explored for their ability to inhibit key signaling pathways, such as FAK and EGFR, and to target specific mutations in cancer cells. The review also discusses the development of next-generation EGFR inhibitors and CDK inhibitors, which are crucial for treating advanced or metastatic cancers. Additionally, pyrimidine-based drugs have been investigated for their potential in targeting microtubules, which are essential components of the cytoskeleton and important targets for anticancer drugs. The review highlights the importance of pyrimidine-based drugs in drug research and development, emphasizing their potential for treating previously untreatable medical conditions.