The positron-emitting radionuclide carbon-11 (¹¹C, t_1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [¹¹C]methyl iodide or [¹¹C]methyl triflate (generated from [¹¹C]carbon dioxide or [¹¹C]methane). Consequently, small molecules that lack an easily substituted ¹¹C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [¹¹C]Carbon dioxide itself, [¹¹C]carbon monoxide, [¹¹C]cyanide, and [¹¹C]phosgene represent alternative reactants to enable ¹¹C-carbonylation. Methodologies developed for preparation of ¹¹C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. ¹¹C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry.