A catheter drive cassette (24, 300) configured to couple to a motor drive base (22, 302) is provided, the catheter drive cassette (24, 300) comprising a housing (42, 316), a first axial drive mechanism (48, 212, 350) supported by the housing (42, 316) configured to releasably engage and drive a guide wire (50, 301) along its longitudinal axis, a second axial drive mechanism (52, 352) supported by the housing (42, 316) configured to releasably engage and drive a catheter device (54, 303) along its longitudinal axis, and a first rotational drive mechanism (56, 96, 326) configured to rotate the guide wire (50, 301) about its longitudinal axis, the first rotational drive mechanism (56, 96, 326) including a rotating structure configured to releasably engage the guide wire (50, 301), the rotating structure configured to apply sufficient force to rotate the guide wire (50, 301) about its longitudinal axis upon rotation of the rotating structure while still permitting the guide wire (50, 301) to be moved axially by the first axial drive mechanism (48, 212, 350), the first and second axial drive mechanisms and the rotational drive mechanism being connectable to a drive being external to the catheter drive cassette (24, 300).