Approximately 37% of aromatic ring-containing small-molecule drugs now feature at least one heteroaromatic unit, and this count is increasing in the new potential clinical trial drugs. In modern medicinal chemistry, replacing planar aromatic rings with C(sp )-rich polycyclic hydrocarbons proved to be beneficial to improve the metabolic stability, solubility, and lipophilicity of potential drug candidates. Structurally rigid bicyclo[n. 1.1]alkanes (n = 1, 2, or 3) and cubanes having welldefined exit-vectors emerged as highly successful bioisosteres of differently substituted benzene rings (Fig. ). In stark contrast, bioisosteric mimetics of heteroaromatic compounds are extremely rare.