Congenital obstructive malformations of the ureter are amongst the most common human birth defects. To date, the etiology of these diseases has remained largely unexplored, which has preempted any rational approach for therapeutic intervention. Here, we describe that obstructive ureter defects can arise from genetic insults affecting various subprograms of ureter development including formation and patterning of the ureteric bud, differentiation of tissue compartments of the ureter, and junction formation with the bladder and pelvis. New experimental findings have highlighted the importance of epithelial-mesenchymal tissue interactions in all of these subprograms and provided unique insights into the molecular nature of the transcriptional regulators and signaling pathways involved.