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Background: Isoquinoline analogs are an important, structurally diverse class of compounds that are extensively used as pharmaceuticals. Derivatives containing the isoquinoline scaffold have become a focus of therapeutic research because of their wide range of biological characteristics. Examples of these drugs, many of which are in clinical application or at the pre-clinical stage, are used to treat a broad swathe of ailments, such as tumors, respiratory diseases, infections, nervous system diseases, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases. Methods: Data were collected from PubMed, Web of Science, and SciFinder, through searches of drug names. Results: At least 38 isoquinoline-based therapeutic drugs are in clinical application or clinical trials, and their chemical structure and pharmacokinetics are described in detail. Conclusion: The isoquinoline ring is a privileged scaffold which is often preferred as a structural basis for drug design, and plays an important role in drug discovery. This review provides a guide for pharmacologists to find effective preclinical/clinical drugs and examines recent progress in the application of the isoquinoline scaffold.