A universal alignment guide for universally positioning an instrument with respect to a bone to facilitate resecting the bone along desired orientations. The alignment guide comprises a spheroidal base and a collar coupled to the base in a manner to allow universal motion of the collar with respect to the base. The base of the alignment guide is attached to a bone anchor implanted in a bone, and the collar is attached to an instrument, such as a resection guide. With respect to a distal femur, the alignment guide facilitates simultaneous positioning and locking of the resection guide in flexion/extension, varus/valgus, internal/external rotation, and proximal/distal orientations.