Phenotypic plasticity pervades organismal development and physiology where it facilitates an enormous range of adaptive responses to novel or stressful environments. Plasticity also impacts evolutionary processes, reducing the probability of population extinction in the face of environmental changes and sometimes increasing speciation rates in developmentally plastic lineages. Despite the adaptive significance of plasticity, organisms are not infinitely plastic; rather they are constrained in the kinds and ranges of environmental changes to which their body parts, organs, and tissues can respond. Understanding the nature, costs, and limits of developmental plasticity requires insight into (i) the developmental-genetic and genomic mechanisms underlying plastic responses as well as (ii) their interplay with ecological and social conditions. In this chapter we review and summarize recent progress in the development of horned beetles as a study system with which to explore the interactions between changing ecological conditions and plastic, genome-wide responses in gene expression and developmental function. In particular, we focus on plastic responses to nutritional variation, which in horned beetles differ widely as a function of body region, sex, and species. We begin by introducing the study system and summarize the developmental-genetic and genomic tool set currently available for horned beetles. We then present recently developed statistical approaches that can be used to guide the design of multi-factorial genome-wide transcriptional comparisons when circumstances prohibit a fully balanced design. We present an example of such an approach in the horned beetle Onthophagus taurus and end by highlighting the growing opportunities for future ecological-genomic studies in horned beetles.