The mitogen-activated protein kinase (MAPK) pathway is crucial for cellular proliferation, growth, and survival. Constitutive activation of this pathway by BRAF mutations can lead to uncontrolled cellular growth and carcinogenesis. Inhibiting BRAF and its downstream substrate MEK has proven effective in controlling tumor growth and proliferation. Over the past decade, several BRAF and MEK inhibitors have been developed and FDA-approved for various cancers, including melanoma, non-small cell lung cancer, anaplastic thyroid cancer, colorectal cancer, and histiocytosis neoplasms. This review covers the development of BRAF and MEK inhibitors, their indications across different cancers, combinations with immunotherapy, associated toxicities, resistance mechanisms, and future directions. Key drugs discussed include vemurafenib, dabrafenib, encorafenib, trametinib, cobimetinib, and binimetinib. The review also highlights the importance of these drugs in personalized medicine.The mitogen-activated protein kinase (MAPK) pathway is crucial for cellular proliferation, growth, and survival. Constitutive activation of this pathway by BRAF mutations can lead to uncontrolled cellular growth and carcinogenesis. Inhibiting BRAF and its downstream substrate MEK has proven effective in controlling tumor growth and proliferation. Over the past decade, several BRAF and MEK inhibitors have been developed and FDA-approved for various cancers, including melanoma, non-small cell lung cancer, anaplastic thyroid cancer, colorectal cancer, and histiocytosis neoplasms. This review covers the development of BRAF and MEK inhibitors, their indications across different cancers, combinations with immunotherapy, associated toxicities, resistance mechanisms, and future directions. Key drugs discussed include vemurafenib, dabrafenib, encorafenib, trametinib, cobimetinib, and binimetinib. The review also highlights the importance of these drugs in personalized medicine.