A robotic catheter system, comprising: a controller including a master input device; an instrument driver in communication with the controller, the instrument driver having a guide instrument interface including a plurality of guide instrument drive elements (44, 244, 260, 262, 270) responsive to control signals generated, at least in part, by the master input device; and an elongate guide instrument (18, 90) having a base, distal end, and a working lumen, the guide instrument base operatively coupled to the guide instrument interface, the guide instrument comprising a plurality of guide instrument control elements (192, 264, 308, 310, 312, 314) operatively coupled to respective guide drive elements (44, 244, 260, 262, 270) and secured to the distal end of the guide instrument, the guide instrument control elements (192, 264, 308, 310, 312, 314) axially moveable relative to the guide instrument (18, 90) such that movement of the guide instrument distal end may be controlled by movement of the master input device, wherein the controller and instrument driver are configured to independently control the guide instrument drive elements (44, 244, 260, 262, 270) and corresponding guide instrument control elements (192, 264, 308, 310, 312, 314) in order to achieve a desired bending of the guide instrument distal end, and wherein the system further comprises a localization system operatively coupled to the controller, the localization system configured to obtain position information of the guide instrument (18, 90), wherein the controller compares the position of the guide instrument (18, 90), based on XYZ position data of the guide instrument (18, 90) from the localization system and through an inverse kinematics calculation of pitch, yaw and extension of the guide instrument (18, 90), with a desired end-point position of filtered desired pitch, yaw and extension of the guide instrument (18, 90) from the master input device, and conducts an integral compensation on the position of the guide instrument (18, 90) with limits on pitch and yaw to integrate away an error, towards the desired end-point position. a controller including a master input device; an instrument driver in communication with the controller, the instrument driver having a guide instrument interface including a plurality of guide instrument drive elements (44, 244, 260, 262, 270) responsive to control signals generated, at least in part, by the master input device; and an elongate guide instrument (18, 90) having a base, distal end, and a working lumen, the guide instrument base operatively coupled to the guide instrument interface, the guide instrument comprising a plurality of guide instrument control elements (192, 264, 308, 310, 312, 314) operatively coupled to respective guide drive elements (44, 244, 260, 262, 270) and secured to the distal end of the guide instrument, the guide instrument control elements (192, 264, 308, 310, 312, 314) axially moveable relative to the guide instrument (18, 90) such that movement of the guide instrument distal end may be controlled by movement of the master input device, wherein the controller and instrument driver are configured to independently control the guide instrument drive elements (44, 244, 260, 262, 270) and corresponding guide instrument control elements (192, 264, 308, 310, 312, 314) in order to achieve a desired bending of the guide instrument distal end, and wherein the system further comprises a localization system operatively coupled to the controller, the localization system configured to obtain position information of the guide instrument (18, 90), wherein the controller compares the position of the guide instrument (18, 90), based on XYZ position data of the guide instrument (18, 90) from the localization system and through an inverse kinematics calculation of pitch, yaw and extension of the guide instrument (18, 90), with a desired end-point position of filtered desired pitch, yaw and extension of the guide instrument (18, 90) from the master input device, and conducts an integral compensation on the position of the guide instrument (18, 90) with limits on pitch and yaw to integrate away an error, towards the desired end-point position.