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A drug’s pKa is the pH at which half of a specific ionizable group is ionized. For weak acids, ionization increases as pH rises above pKa; for weak bases, it increases as pH falls below pKa. The Henderson–Hasselbalch equation describes the relationship between pH, pKa, and the ionized-to-unionized ratio. In general, unionized forms cross membranes more readily, while ionized forms dissolve better in aqueous media. These principles help explain pH-dependent absorption, salt selection, and formulation decisions. Molecules with multiple ionizable groups can have multiple pKa values, while zwitterions have an isoelectric point at which their net charge is zero. The lesson also distinguishes logP from pH-dependent logD and introduces how ionization relates to protein binding and drug design.