I use Excel extensively at work and this is something that has bugged me for a long time. Do you ever find that the scroll bar tries to scroll the entire spreadsheet instead of just the area where the data is? This is because the 'used range' has become confused somehow.

To manually reset the used range:
Select the last cell that contains data in the worksheet

To delete any unused rows:
Move down one row from the last cell with data.
Hold the Ctrl and Shift keys, and press the Down Arrow key
Right-click in the selected cells, and, from the shortcut menu, choose Delete
Select Entire Row, click OK.

To delete any unused columns:
Move right one column from the last cell with data.
Hold the Ctrl and Shift keys, and press the Right Arrow key
Right-click in the selected cells, and, from the shortcut menu, choose Delete Select Entire Column, click OK.

Save the file. Note: In older versions of Excel, you may have to Save, then close and re-open the file before the used range is reset.

Thanks to http://www.contextures.com/xlfaqApp.html#Unused