In this paper we classify weak Fano varieties that can be obtained by blowing-up general points in prime Fano varieties. We also classify spherical blow-ups of Grassmannians in general points, and we compute their effective cone. These blow-ups are, in particular, Mori dream spaces. Furthermore, we compute the stable base locus decomposition of the blow-up of a Grassmannian in one point, and we show how it is determined by linear systems of hyperplanes containing the osculating spaces of the Grassmannian at the blown-up point, and by the rational normal curves in the Grassmannian passing through the blown-up point.Throughout the paper X will be a normal projective variety over an algebraically closed field of characteristic zero. We denote by N 1 (X) the real vector space of R-Cartier divisors modulo numerical equivalence. The nef cone of X is the closed convex cone Nef(X) ⊂ N 1 (X) generated by classes of nef divisors. The movable cone of X is the convex cone Mov(X) ⊂ N 1 (X) generated by