Genome assemblies that are accurate, complete, and contiguous are essential for identifying important structural and functional elements of genomes and for identifying genetic variation. Nevertheless, most recent genome assemblies remain incomplete and fragmented. While long molecule sequencing promises to deliver more complete genome assemblies with fewer gaps, concerns about error rates, low yields, stringent DNA requirements, and uncertainty about best practices may discourage many investigators from adopting this technology. Here, in conjunction with the gold standard Drosophila melanogaster reference genome, we analyze recently published long molecule sequencing data to identify what governs completeness and contiguity of genome assemblies. We also present a meta-assembly tool for improving contiguity of final assemblies constructed via different methods. Our results motivate a set of preliminary best practices for assembly, a ‘missing manual’ that guides key decisions in building high quality de novo genome assemblies, from DNA isolation to polishing the assembly.