Management of asthma with long-acting β2-adrenergic receptor agonists and corticosteroids is exceptionally effective for the majority of asthma patients. However, corticosteroid insensitivity or resistance remains a significant clinical problem for a significant proportion of patients, requiring the investigation of new potential therapeutics for asthma. Histone deacetylase inhibitors represent a different class of compounds that have been evaluated for their potential antiasthmatic effects. Although accumulating evidence is indicating beneficial effects in rodent models of allergic airways disease, the potential use of histone deacetylase inhibitors in asthma remains controversial given their mechanisms of action. The aim of this paper is to provide an overview of histone deacetylases and pharmacological modifiers of these enzymes. The discussion represents a balanced account of the emerging evidence indicating the beneficial effects of histone deacetylase inhibitors in inflammatory lung diseases. The potential problems associated with the use of this class of compounds in asthma are also carefully considered.