Sponges and their associated microbiota are well known to produce a large diversity of natural products, also called specialized metabolites. In addition to their potential use in the pharmaceutical industry, these rather species-specific compounds may help in the classification of some particular sponge groups. We review herein compounds isolated from haplosclerid sponges (Class Demospongia, Order Haplosclerida) in order to help in the revision of this large group of marine invertebrates. We focus only on 3-alkylpyridine derivatives and polyacetylenic compounds, as these two groups of natural products are characteristic of haplosclerid species and are highly diverse. A close collaboration between chemists and biologists is required in order to fully apply chemotaxonomical approaches, and whenever possible biological data should include morphological and molecular data and some insight into their microbial abundance.