Physicochemical descriptors commonly used to define "drug-likeness" and ligand efficiency measures are assessed for their ability to differentiate marketed drugs from compounds reported to bind to their efficacious target or targets. Using ChEMBL version 26, a data set of 643 drugs acting on 271 targets was assembled, comprising 1104 drug-target pairs having ≥100 published compounds per target. Taking into account changes in their physicochemical properties over time, drugs are analyzed according to their target class, therapy area, and route of administration. Recent drugs, approved in 2010-2020, display no overall differences in molecular weight, lipophilicity, hydrogen bonding, or polar surface area from their target comparator compounds. Drugs are differentiated from target comparators by higher potency, ligand efficiency (LE), lipophilic ligand efficiency (LLE), and lower carboaromaticity. Overall, 96% of drugs have LE or LLE values, or both, greater than the median values of their target comparator compounds.