Why am I being ignored by agents and publishers? Should I give up?

First, if you feel that writing is your vocation—something you’re compelled to do and will continue to do whether you are ever published during your lifetime or not—you shouldn’t give it up. There are many reasons agents and publishers might be ignoring you, and none of them is personal. While rejections from agents and publishers might indicate that you are not yet a skilled enough writer to rise above the fray, they might also indicate that agents and publishers don’t think your work will sell. Finding an agent or a publisher is a mysterious process that involves plenty of things that are out of your control, including timing, subjectivity, and luck.

Many currently successful writers have struggled with the writing process and with rejection. My opinion is that the best tools a writer can develop are determination and perseverance. Determine to be the best writer you can be, and work hard at it, and don’t give up. If you're feeling discouraged, I recommend reading Betsy Lerner's book The Forest for the Trees: An Editor’s Advice to Writers. Lerner also has a blog called The Forest for the Trees.