The first paragraph of your letter should include information on why you are writing. Mention the position you are applying for. Include the name of a mutual contact, if you have one. Be clear and concise regarding your request. Convince the reader that they should grant the interview or appointment you requested in the first paragraph.
The next section of your cover letter should describe what you have to offer the employer. Make strong connections between your abilities and their needs. Mention specifically how your skills and experience match the job you are applying for. Remember, you are interpreting your resume, not repeating it. Try to support each statement you make with a piece of evidence. Use several shorter paragraphs or bullets rather than one large block of text.
Conclude your cover letter by thanking the employer for considering you for the position. Include information on how you will follow-up. State that you will do so and indicate when (one week's time is typical). You may want to reduce the time between sending out your resume and follow up if you fax or e-mail it.