Methods and apparatus are provided for disruption/destruction of subcutaneous structures in a mammalian body for the treatment of skin irregularities, and other disorders such as excess adipose tissue, cellulite, and scarring. Devices and methods include energy mediated applicators, microneedles, catheters and subcutaneous treatment devices for applying a treatment non-invasively through the skin, less invasively through the skin, or minimally invasively via a subcutaneous approach. Various agents to assist or enhance the procedures are also disclosed.