View this article online at wileyonlinelibrary.com.The use of palladium complexes in catalyzing the cross-coupling of halogenated quinolines with various organometalic reagents has led to the development of radically new methods of synthesizing novel substituted quinoline derivatives. The focus of this review is on the application of the following palladium-catalyzed reactions of halogenated quinolines with organometalic reagents to afford substituted quinoline derivatives: Kumada, Stille, Negishi, Sonogashira, Suzuki, Heck, and Hiyama cross-coupling reactions. Scheme 4. Palladium-catalyzed coupling of the 4-bromoquinoline derivatives with zinc cyanide. Reagents and conditions: (i) Zn(CN) 2 , Pd(PPh 3 ) 4 , DMF, 80°C; (ii) Pyr·HBr, 200°C. Scheme 3. Palladium-catalyzed Negishi cross-coupling of quinolyl zinc iodides with organoiodides. Reagents and conditions: (i) Zn, DMA; (ii) Pd(dba) 2 , P(o-furyl) 3 , THF, room temperature or heat (for 13c, e, and f).4 M. Scheme 8. Successive Negishi cross-coupling of 2,6-dibromoquinoline with organozinc reagents. Reagents and conditions: (i) Pd(OAc) 2 , P(o-furyl) 3 , PhMe/DMA; (ii) [ 14 C]-MeZnI; NiCl 2 (dppp); THF. Scheme 9. Palladium-phosphinous acid-catalyzed alkynylation of 4-chloroquinoline. Reagents and conditions: (i) POPd, TBAB, NaOH, CuI, H 2 O, 5 h. Scheme 10. One-pot palladium/CuI-catalyzed dialkynylation of 2,4-dichloroquinoline. Reagents and conditions: (i) Pd/C, PPh 3 , CuI, NEt 3 , water, 80-85°C. 6 M.