Do your research and prepare a list of publishers to approach. Don't limit yourself to one. If more than one publisher is interested in your book, you'll be able to negotiate a better deal.
Make sure the publisher prints the type of book you've written. Don't take a novel to a non-fiction publisher or a work of history to a romance company. Use resources like Books in Print, available at your library, for your research.
Have paperback advanced reading copies or finished books made. Send them to publishers with an information packet that includes a synopsis, number of pages and information on whether the book will be illustrated. Include a brief autobiography and your credentials.
Write a cover letter for your book briefly introducing yourself. Mention that you'll be calling to follow up and offer to provide any other information the publisher needs. Include your contact information, the marketing you've done and testimonials from people who have read the manuscript.
Follow up with publishers by calling and visiting if possible. Listen to their critique of your book and their reasons for not publishing. Ask if you can make changes that would make the book more salable. Learn from what the publishers have told you.
Create buzz for your book by sending copies to local television stations and book reviewers. Make yourself available for interviews. Go to bookstores and talk to the buyers. Ask them to mention your book when they meet with publisher's sales reps.
Keep trying. There are thousands of publishers around the world. One of them will publish you. Be optimistic and use a fresh approach with each publisher.