We present a versatile density functional approach (DFT) for calculating the
depletion potential in general fluid mixtures. In contrast to brute force DFT,
our approach requires only the equilibrium density profile of the small
particles {\em before} the big (test) particle is inserted. For a big particle
near a planar wall or a cylinder or another fixed big particle the relevant
density profiles are functions of a single variable, which avoids the numerical
complications inherent in brute force DFT. We implement our approach for
additive hard-sphere mixtures. By investigating the depletion potential for
high size asymmetries we assess the regime of validity of the well-known
Derjaguin approximation for hard-sphere mixtures and argue that this fails. We
provide an accurate parametrization of the depletion potential in hard-sphere
fluids which should be useful for effective Hamiltonian studies of phase
behavior and colloid structure