This study presents a new methodology for designing and analyzing three‐dimensional sampling networks for groundwater quality monitoring. Sampling design is represented in the frequency domain as a transfer function acting on the concentration spectrum to provide the sampling error variance, which is used as a measure of sampling performance. The presented methodology does not require numerical solution of either flow or transport equations; it operates directly on the statistics of the concentration field evaluated using a spectral representation. It also separates sampling design issues from the statistics of the aquifer properties, allowing better understanding of the influence of the subsurface characteristics on sampling error and therefore on sampling network design. The results show that sampling of groundwater quality should be viewed as a three‐dimensional activity with two major design parameters: spatial spacing between wells (Δli, i = 1, 2, 3) and total number of wells. In the horizontal plane there is a clear need for anisotropy in spacing between wells with larger spacing needed in the direction of the mean flow than in the perpendicular direction. The sampling anisotropy ratio Δl1/Δl2 is found to be a function of the correlation structure of the hydraulic conductivity field and number of wells. The presented example demonstrates how sampling network design guidelines can be developed as functions of the statistical structure of the hydraulic conductivity field and other transport parameters.