During the performance of dissolution tests with immediate and controlled-release talinolol tablets it was detected that the type of the buffer used as dissolution medium had a strong influence on the solubility and the dissolution behavior of the drug. It was proven that talinolol appeared in different crystal structures with strongly differing solubilities when pure water, acetate, or phosphate buffers were employed as dissolution media. The resulting crystal structures were characterized by means of light microscopy, differential scanning calorimetry, and X-ray powder diffraction. All methods were adjuvant to detect changes in talinolol crystal structures. The different solubility and dissolution properties of the talinolol salts or modifications may be viewed as a source for its incomplete and variable bioavailability. Furthermore, the food effect, described in the literature, that leads to a decrease in talinolol absorption, could be due to changes in the composition of gastrointestinal fluids leading to different talinolol crystal structures. Furthermore, it was detected that the addition of sodium chloride increases talinolol solubility and accelerates its dissolution from controlled-release tablets at concentrations between 0% and 1.25%, while an addition of sodium dodecylsulfate (SDS) as surfactant only had a solubility-improving effect at concentrations > 0.75%. At lower concentrations SDS decreased the solubility of talinolol and notably decelerated its release from controlled-release tablets.