We consider the problem of registering (aligning) two images to sub-pixel accuracy by optimization of objective functions constructed from the images' intensity values. We show that some widely used interpolation methods can introduce multiple local optima in the energy of the interpolated image which, if not counter-balanced by other terms, can cause local optima in registration objective functions including the sum of squared differences, cross correlation, and mutual information. We discuss different solutions to address the problem based on high degree B-spline interpolation, low pass filtering the images, and stochastic integration. Numerical examples using synthetic and real signals and images are shown.