Some types of nonprofits face unique issues due to the type of work they do. Operating a childcare agency may involve certification requirements; working with ex-offenders may expose an organization to added liability risk, etc. State or national trade associations can often provide information on these specifics.
Nonprofits that earn in excess of $1000 per year from business activity unrelated to the charitable or educational mission of the agency may be required to submit additional paperwork and/or pay taxes on this income. The IRS website provides more information about the Unrelated Business Income Tax Rules and Requirements.