Methods and apparatus for off-axis visualization are described herein. An endoluminal tissue manipulation assembly is disclosed which provides for a stable endoluminal platform and which also provides for effective triangulation of tools. Such an apparatus may comprise an optionally shape-lockable elongate body defining a longitudinal axis and adapted for endoluminal advancement in a patient body, at least one articulatable visualization lumen disposed near or at a distal region of the elongate body, the at least one articulating visualization lumen being adapted to articulate off-axis relative to a longitudinal axis of the elongate body, and at least one articulatable tool arm member disposed near or at the distal region of the elongate body, the at least one articulatable tool arm member being adapted to articulate off-axis and manipulate a tissue region of interest.