It is well known that the permeability has a tensor character. In practical applications, this is accounted for by the introduction of three principal permeabilities - three scalars - and three mutually orthogonal principal axes. In this paper, it is investigated whether this is always the exact way of describing anisotropy and, if not, what the consequences of the principal axes approximation are for flow and transport. First, it is shown that spatial upscaling may result in nonsymmetric large-scale permeability tensors, for which principal axes do not exist. However, it is possible to define generalized principal axes: three principal axes for the flux and three for the pressure gradient, with only three principal permeabilities. Since nonsymmetric permeability tensors are undesirable in practical applications, an approximation method making the nonsymmetric permeability symmetric is introduced. The important conclusion is then that the exact large-scale flux and large-scale pressure gradient do not have the same directions as the approximate Aux and approximate pressure gradient. A practical consequence is that the principal axes approximation results in a difference between flux and transport direction. When considering miscible displacement or transport of mass dissolved in groundwater, the velocity component normal to the flux direction may be considered as a contribution to the transverse macro dispersion.