<p>The non-bonded interaction between the positive electrostatic potential associated with a σ*-orbital (the σ hole) of a substituted carbon atom and an atom with a lone pair of electrons is referred to as tetrel bonding and can be expressed in both intermolecular and intramolecular manifolds. Intermolecular tetrel bonding can contribute to the inventory of interactions that convene protein-ligand complexes while intramolecular tetrel bonds can influence the conformation of a molecule. While the energy associated with a carbon-based tetrel bond is calculated to be of a modest value, ranging from ~5 kcal/mole for a close contact between optimal partners to ~1 kcal/mole for a more relaxed and what is perhaps the more typical interaction, the prevalence of carbon tetrel bonding in drug design may be underappreciated. The energy of a carbon-based σ-hole tetrel bonding interaction has been equated with that calculated for the more prominent n→π* multipolar-type of tetrel bonding interaction or a C-H→π bond, both of which are recognized as interactions of value in drug design. In this review, we provide a perspective on the evidence in support of intermolecular and intramolecular σ-hole tetrel bonding interactions in the context of geometric parameters associated with drug and drug-like molecule structures deposited in the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB).</p><p></p>