State-of-the-art microscopy techniques (e. g., atomic force microscopy, scanning-tunneling microscopy, and optical tweezers) are sensitive to atomic-scale (100 pm) displacements. Yet, sample drift limits the ultimate potential of many of these techniques. We demonstrate a general solution for sample control in 3D using back-scattered detection (BSD) in both air and water. BSD off a silicon disk fabricated on a cover slip enabled 19 pm lateral localization precision (Delta f = 0.1 -50 Hz) with low crosstalk between axes (<= 3%). We achieved atomic-scale stabilization (88, 79, and 98 pm, in x, y, and z, respectively; Delta f = 0.1 -50 Hz) and registration (approximate to 50 pm (rms), N = 14, Delta t = 90 s) of a sample in 3D that allows for stabilized scanning with uniform steps using low laser power (1 mW). Thus, BSD provides a precise method to locally measure and thereby actively control sample position for diverse applications, especially those with limited optical access such as scanning probe microscopy, and magnetic tweezers. (C) 2007 Optical Society of America.