The crossing number, cr(G), of a graph G is the least number of crossing points in any drawing of G in the plane. According to the Crossing Lemma of Ajtai, Chvátal, Newborn, Szemerédi [ACNS82] and Leighton [L83], the crossing number of any graph with n vertices and e > 4n edges is at least constant times e/n. Apart from the value of the constant, this bound cannot be improved. We establish some stronger lower bounds, under the assumption that the distribution of the degrees of the vertices is irregular. In particular, we show that if the degrees of the vertices are d1 ≥ d2 ≥ . . . ≥ dn, then the crossing number satisfies cr(G) ≥ c1 n ∑ n i=1 id3i − c2n , and that this bound is tight apart from the values of the constants c1, c2 > 0. Some applications are also presented.