Alpha-emitting radionuclides are gaining attention in oncology for their unique physical properties, such as high linear energy transfer (LET) and short range in tissue, which enable targeted therapy at the single-cell level. This review discusses the current status and future perspectives of alpha-emitting radionuclides, focusing on their production, chemical conjugation, clinical applications, and challenges. Actinium-225 (²²⁵Ac) is a key radionuclide due to its high LET and short range, making it effective for targeting cancer cells. However, its production is limited, and alternative methods are being explored. The development of matched radionuclide pairs, such as ²²⁵Ac with lanthanum-133, allows for both diagnostic imaging and therapeutic applications. Chelators like DOTA and macropa are used to stabilize the radionuclides and enhance their targeting efficiency. Lead isotopes, such as ²¹²Pb and ²⁰³Pb, are also being investigated for their ability to generate alpha emitters. Astatine-211 (²¹¹At) is another promising alpha emitter with high therapeutic potential. Clinical trials are ongoing for various alpha-emitting radionuclides, including ²²³Ra, ²¹³Bi, and ²²⁵Ac, with promising results in treating cancers such as prostate cancer and neuroendocrine tumors. Challenges include optimizing pharmacokinetics, minimizing off-target effects, and ensuring safety. Future directions involve combining alpha therapy with other treatments and improving imaging techniques for better therapeutic monitoring. Overall, alpha-emitting radionuclides offer a promising approach for targeted cancer therapy with high efficacy and minimal side effects.Alpha-emitting radionuclides are gaining attention in oncology for their unique physical properties, such as high linear energy transfer (LET) and short range in tissue, which enable targeted therapy at the single-cell level. This review discusses the current status and future perspectives of alpha-emitting radionuclides, focusing on their production, chemical conjugation, clinical applications, and challenges. Actinium-225 (²²⁵Ac) is a key radionuclide due to its high LET and short range, making it effective for targeting cancer cells. However, its production is limited, and alternative methods are being explored. The development of matched radionuclide pairs, such as ²²⁵Ac with lanthanum-133, allows for both diagnostic imaging and therapeutic applications. Chelators like DOTA and macropa are used to stabilize the radionuclides and enhance their targeting efficiency. Lead isotopes, such as ²¹²Pb and ²⁰³Pb, are also being investigated for their ability to generate alpha emitters. Astatine-211 (²¹¹At) is another promising alpha emitter with high therapeutic potential. Clinical trials are ongoing for various alpha-emitting radionuclides, including ²²³Ra, ²¹³Bi, and ²²⁵Ac, with promising results in treating cancers such as prostate cancer and neuroendocrine tumors. Challenges include optimizing pharmacokinetics, minimizing off-target effects, and ensuring safety. Future directions involve combining alpha therapy with other treatments and improving imaging techniques for better therapeutic monitoring. Overall, alpha-emitting radionuclides offer a promising approach for targeted cancer therapy with high efficacy and minimal side effects.