Cocrystal formation of chlorothiazide (ctz) was screened with a variety of coformers with carboxyl, amide, hydroxyl, sulfonamide, pyridine, amidine, and amine functional groups. New cocrystals with acetamide (aca), benzamide (bza), propionamide (ppa), caprolactam (cap), carbamazepine (cbz), nicotinamide (nia), isonicotinamide (ina), hexamethylenetetramine (hma), 4,4'-bipyridine (bipy), 1,2-di(4-pyridyl)ethylene (ebipy), 2-hydroxypyridine (hyp), 1,3-di(4-pyridyl)propane (pbipy) and pyrazine (pyr) as well as a benzamidinium (bzamH(+)) salt were obtained by mechanical grinding and liquid-assisted grinding and identified by powder X-ray diffraction. The structures of ctz-bza, ctz-cbz, ctz-ina, ctz-nia, ctz-hma, ctz-bipy, ctz-ebipy, ctzpbipy, and (bzamH(+)) (ctz(-)) were determined by single-crystal X-ray diffraction. Analysis of the hydrogen bonding motifs showed that in all cocrystal structures except for ctz-bipy, the NHsuifonamide center dot center dot center dot N (SO2)=C catemer synthon of ctz form I is replaced by ctz-coformer heterosynthons. The dissolution behavior and relationship between dissolution rate, packing index, and lattice energy of the cocrystals is described. To understand why no cocrystals with carboxylic acids formed, a motif search of the Cambridge Structural Database (CSD) was carried out.