The [14C]carbonylation reaction is a very powerful method of incorporating C‐14 into a drug molecule late in a radiochemical synthesis. The first and perhaps most critical step in [14C]carbonylation reactions is the generation of 14CO and its subsequent delivery to the reaction flask. There are three published methods for generating 14CO: conversion of 14CO2 with Zn at 400°C, pyrolysis of Ca14CO3, and dehydration of NaO 142CH. Additionally, a newly published method for the in situ carbonylation of aryl and vinyl halides to give acids has been investigated using NaO 142CH as the labeled precursor. Finally, the application of 14CO in Pd‐catalyzed [14C]carbonylation reactions will be discussed. Copyright © 2010 John Wiley & Sons, Ltd.