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Administration of steroidal drugs is hampered by their very low solubilities in water. β-Cyclodextrin and β-cyclodextrin derivatives can solubilize steroids and improve bio-availability of these hydrophobic APIs. A systematic overview of the achievable solubility enhancements of various steroids, testosterone, estradiol, progesterone, hydrocortisone, prednisone, dexamethasone, and finasteride, is provided. Beside the spatial fit of the steroid within the cyclodextrin cavity also hydrophilic substituents at the cyclodextrin framework play an important role in the extent of solubilization observed. Uniformly substituted anionic heptakis-6-sulfoethylsulfanyl-6-deoxy-β-cyclodextrin (HSES) performed best, reaching complexation efficiencies of 60–90 mol% for most steroids. Two neutral β-cyclodextrin thioethers, heptakis-6-methylsulfanyl-6-deoxy-2-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)]-β-CD (HTMT) and heptakis-6-thioglyceryl-6-deoxy-β-CD (HTG) showed gender selectivity in binding of hormons: HTMT was selective for testosterone, while HTG was selective for estradiol. Solubilization is mainly due to complexation of the A and B rings as well as C and D rings of the steroid framework as demonstrated by ROESY NMR spectroscopy.