We investigate the algorithmics of subtyping in the presence of nominal inheritance and variance for generic types, as found in Java 5, Scala 2.0, and the .NET 2.0 Intermediate Language. We prove that the general problem is undecidable and characterize three different decidable fragments. From the latter, we conjecture that undecidability critically depends on the combination of three features that are not found together in any of these languages: contravariant type constructors, class hierarchies in which the set of types reachable from a given type by inheritance and decomposition is not always finite, and class hierarchies in which a type may have multiple supertypes with the same head constructor. These results settle one case of practical interest: subtyping between ground types in the .NET intermediate language is decidable; we conjecture that our proof can also be extended to show full decidability of subtyping in .NET. For Java and Scala, the decidability questions remain open; however, the proofs of our preliminary results introduce a number of novel techniques that we hope may be useful in further attacks on these questions.