This review discusses the practical considerations and (pre-)clinical perspectives of implementing Ac-225 labelled radiopharmaceuticals. Ac-225 is a promising alpha emitter for targeted alpha therapy (TAT) due to its high linear energy transfer (LET) and short tissue penetration, leading to localized dose effects and high local toxicity. However, its use presents several challenges, including the need for precise labelling conditions, purity of the radionuclide source, chelator selection, and quenchers to avoid radiolysis. The high toxicity of Ac-225 necessitates strict health physics regulations, limiting practical handling and quantities used for quality control (QC). Ac-225 is produced from Th-229, with alternative methods including spallation reactions and irradiation of Ra-226. The production of Ac-225 is limited by the availability of Th-229 and the need for high-energy proton beams. The radiolabelling of Ac-225 requires careful selection of chelators, with DOTA being the most commonly used. Other chelators like Macropa and Crown show promise for complexation with Ac-225. The biological vectors used for Ac-225 include monoclonal antibodies, nanobodies, and small molecules, each with different biodistribution and toxicity profiles. The radiolabelling process involves optimizing conditions for clinical implementation, including the use of reduced activity and maintaining quencher concentrations. The detection of Ac-225 is challenging due to its high toxicity and the need for equilibrium with daughter nuclides. Quality control (QC) techniques such as radio-TLC, HPLC, and gamma counters are used to assess the radiochemical yield (RCY) and purity (RCP). The equilibrium between Ac-225 and its daughter nuclides (Fr-221, Bi-213) is crucial for accurate measurements, requiring a minimum of six half-lives for Fr-221 to achieve equilibrium. The clinical use of Ac-225 requires strict safety measures, including the use of fume hoods, gloveboxes, and dedicated laboratories to minimize contamination risks. The preparation of clinical Ac-225 radiopharmaceuticals involves the use of non-GMP Ac-225, GMP-grade pharmaceuticals, and solutions. The radiopharmaceuticals must be prepared in a closed system to ensure safety and prevent contamination. The use of Ac-225 in clinical settings is limited by the availability of the radionuclide and the need for specialized equipment and protocols. Despite these challenges, Ac-225 shows promise for targeted alpha therapy, particularly in the treatment of cancers such as prostate cancer and neuroendocrine tumors.This review discusses the practical considerations and (pre-)clinical perspectives of implementing Ac-225 labelled radiopharmaceuticals. Ac-225 is a promising alpha emitter for targeted alpha therapy (TAT) due to its high linear energy transfer (LET) and short tissue penetration, leading to localized dose effects and high local toxicity. However, its use presents several challenges, including the need for precise labelling conditions, purity of the radionuclide source, chelator selection, and quenchers to avoid radiolysis. The high toxicity of Ac-225 necessitates strict health physics regulations, limiting practical handling and quantities used for quality control (QC). Ac-225 is produced from Th-229, with alternative methods including spallation reactions and irradiation of Ra-226. The production of Ac-225 is limited by the availability of Th-229 and the need for high-energy proton beams. The radiolabelling of Ac-225 requires careful selection of chelators, with DOTA being the most commonly used. Other chelators like Macropa and Crown show promise for complexation with Ac-225. The biological vectors used for Ac-225 include monoclonal antibodies, nanobodies, and small molecules, each with different biodistribution and toxicity profiles. The radiolabelling process involves optimizing conditions for clinical implementation, including the use of reduced activity and maintaining quencher concentrations. The detection of Ac-225 is challenging due to its high toxicity and the need for equilibrium with daughter nuclides. Quality control (QC) techniques such as radio-TLC, HPLC, and gamma counters are used to assess the radiochemical yield (RCY) and purity (RCP). The equilibrium between Ac-225 and its daughter nuclides (Fr-221, Bi-213) is crucial for accurate measurements, requiring a minimum of six half-lives for Fr-221 to achieve equilibrium. The clinical use of Ac-225 requires strict safety measures, including the use of fume hoods, gloveboxes, and dedicated laboratories to minimize contamination risks. The preparation of clinical Ac-225 radiopharmaceuticals involves the use of non-GMP Ac-225, GMP-grade pharmaceuticals, and solutions. The radiopharmaceuticals must be prepared in a closed system to ensure safety and prevent contamination. The use of Ac-225 in clinical settings is limited by the availability of the radionuclide and the need for specialized equipment and protocols. Despite these challenges, Ac-225 shows promise for targeted alpha therapy, particularly in the treatment of cancers such as prostate cancer and neuroendocrine tumors.