Recent estimates place technical recoverable reserves of natural gas from the Marcellus Shale at approximately 500 tcf. Development is anticipated to consist primarily of long-reach horizontal wells drilled from multi-well pads with each well stimulated using multi-stage slickwater hydraulic fracturing. Currently, it appears likely that disposal via Class II brine water disposal wells will be an important option for managing water produced from Marcellus Shale wells over the long-term. This paper is structured toward brine disposal issues in Appalachia and associated Marcellus Shale development issues. Many issues come into play with both the siting and the permitting of Class II disposal wells in the Appalachians. Currently, the limited number of existing disposal wells in the region along with geologic challenges makes developing new disposal wells a complex process. Well siting of injection wells must address a variety of environmental and access considerations, especially where water will be trucked to the well. Permitting must consider issues such as calculation of the ‘zone of endangering influence", which becomes more complicated in tight or fractured receiving zones. Gaining approval for well testing and other well drilling and completion activities can be different from western or mid-continent states, so upfront planning is critical. This paper will include a review of the regulatory environment in the region, permitting timeframes, regulatory and permitting requirements, formations being considered for brine water disposal and the associated challenges.