Neuromodulation catheters with shafts for enhanced flexibility and control and methods of making and using the catheters. A neuromodulation catheter can include an elongated shaft having a distal end portion and a mandrel extending at least along the distal end portion. The mandrel can have an at least substantially solid core. The neuromodulation catheter can further include a transition member and a neuromodulation assembly coupled to the transition member. The transition member can have a proximal portion, a distal portion, and a guide wire lumen extending through the proximal and distal portions. The neuromodulation assembly can extend distally from the distal portion of the transition member, and the mandrel can extend proximally from the proximal portion of the transition member.