Association mapping has successfully identified common SNPs associated with many diseases. However, the inability of this class of variation to account for most of the supposed heritability has led to a renewed interest in methods - primarily linkage analysis - to detect rare variants. Family designs allow for control of population stratification, investigations of questions such as parent-of-origin effects and other applications that are imperfectly or not readily addressed in case-control association studies. This article guides readers through the interface between linkage and association analysis, reviews the new methodologies and provides useful guidelines for applications. Just as effective SNP-genotyping tools helped to realize the potential of association studies, next-generation sequencing tools will benefit genetic studies by improving the power of family-based approaches.